Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality

Abstract

The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes; mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%); antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p <0.01); 61 (37.7%) of cases affected patients without HMs or transplantation. Antifungal therapy was administered to 93.2% of patients (median 68 days, interquartile range 19-275), and adjunctive surgery was performed in 58.6%. The all-cause 90-day mortality was 44.4%; HMs and intensive-care admission were the strongest predictors of death (both p <0.001). Survival varied by fungal group, with the risk of death being significantly lower in patients with dematiaceous mould infections than in patients with other non-Aspergillus mould infections. Non-Aspergillus IFD affected diverse patient groups, including non-immunocompromised hosts and those outside traditional risk groups; therefore, definitions of IFD in these patients are required. Given the high mortality, increased recognition of infections and accurate identification of the causative agent are required.

Role of Antifungal Susceptibility Testing in Non-Aspergillus Invasive Mold Infections

“…Unexpectedly, we found the MIC value of the first-line antifungal drug to be the most important factor in predicting response to therapy, an association that was not demonstrated previously (9)(10)(11)(12). It should be emphasized that prior studies assessing predictors of NAIMI focused on overall mortality as an outcome, whereas we specifically assessed response to therapy based on clinical and radiological signs according to EORTC-MSG definitions (8).…”

Performance of Matrix-Assisted Laser Desorption Ionization−Time of Flight Mass Spectrometry for Identification of Aspergillus, Scedosporium, and Fusarium spp. in the Australian Clinical Setting

“…Although Scedosporium prolificans is represented in the Bruker library, only 1/4 isolates was identified to the species level. Scedosporiosis is the second most common nonAspergillus mold infection in Australia with 24% of infections due to S. aurantiacum (19,21,29). Adoption of our database in other Australian centers has the potential to remove reliance on molecular approaches to identify Scedosporium to the species level, overcoming the limitations of other dedicated Scedosporium databases that utilize different software, thus limiting their wider application (8,12,30).…”

“…Given the prior poor performance of the Bruker Filamentous Fungi Library v1.0 (Bruker Daltonics, Bremen, Germany) for mold identification using the manufacturer-recommended broth-based protein extraction methods (in our laboratory Ͼ50% of isolates were not identified; internal data) and because the geographic generalizability of in-house-built databases is not yet known, we hypothesized that a MS library of molds relevant to our region (17)(18)(19)(20)(21) will improve identification. Here, we constructed an in-house database containing 117 strains (see Table S1 in the supplemental material) covering 28 species of Aspergillus, Scedosporium, and Fusarium encountered in Australia.…”

Discrimination of Aspergillosis, Mucormycosis, Fusariosis, and Scedosporiosis in Formalin-Fixed Paraffin-Embedded Tissue Specimens by Use of Multiple Real-Time Quantitative PCR Assays

“…T he frequency of invasive fungal diseases (IFDs) has increased significantly over the past 3 decades, and they are associated with excessive morbidity and mortality in immunocompromised hosts, patients hospitalized with severe underlying diseases (e.g., acute myelogenous leukemia), those requiring complex surgical procedures (e.g., trauma patients), and individuals who require support in intensive care units (1)(2)(3)(4)(5).…”

“…However, the epidemiology of IFDs due to filamentous fungi has been expanded well beyond A. fumigatus, including non-fumigatus species of Aspergillus, the mucormycetes, Fusarium and Scedosporium species, and a wide variety of melanized fungi (4,7).…”